Studies on the peripheral pharmacology of fenazoxine, a potential antidepressant drug

1 . The action of fenazoxine, a cyclized analogue of orphenadrine, has been studied on peripheral tissues innervated by adrenergic and cholinergic nerves. The hypothesis that cyclization of the alkyl amino chain of orphenadrine results in a molecule which retains the noradrenaline sensitizing action of orphenadrine but lacks the antimuscarinic activity has been investigated. 2 . The antimuscarinic activity of fenazoxine, on guinea pig ileum, was approximately 1/30 that of orphenadrine. 3 . Fenazoxine, desmethylimipramine and cocaine potentiated the response to noradrenaline and sympathetic nerve stimulation on the cat nictitating membrane, isolated rabbit ear artery and isolated driven atrial strip preparations. 4 . On the driven atrial strip preparation, fenazoxine at concentrations of 5 × 10 −7 M and 1 × 10 −6 M produced a small potentiation of the inotropic response to isoprenaline. At 5 × 10 −6 M and 5 × 10 −5 M fenazoxine antagonized the inotropic response to tyramine. 5 . Chronic denervation of the cat nictitating membrane abolished the potentiating action of fenazoxine. 6 . The results presented suggest that fenazoxine inhibits the uptake of catecholamines in a manner similar to that reported for desmethylimipramine and cocaine. 7 . Evidence is also presented which suggests that fenazoxine, like desmethylimipramine, possesses anti‐noradrenaline activity at higher concentrations.